Characterisation of human steroid hormone transport mediated by Cdr1p, a multidrug transporter of Candida albicans, belonging to the ATP binding cassette super family.
Cdr1p, a multidrug transporter from a pathogenic yeast Candida albicans, confers resistance to several unrelated drugs including anti-Candida drugs. We demonstrate that Cdr1p can specifically transport human steroid hormones namely beta-estradiol and corticosterone. Saccharomyces cerevisiae transformant S-12, harbouring the CDR1 gene, accumulated about 3-fold less [3H] beta-estradiol and about 2-fold less [3H]corticosterone than the non-transformed strain. When CDR1 was expressed in AD strain (AD-CDR1) which had seven ATP binding cassette (ABC) superfamily of putative transporter genes disrupted, the net accumulation of these hormones as compared to S-12 was significantly lower. Efflux of beta-estradiol and corticosterone was inhibited by a 100-fold higher (200 nM) concentration of beta-estradiol, corticosterone, ergosterol or dexamethasone, but progesterone which could not be transported by Cdr1p did not affect the efflux and thus accumulation. Interestingly, some of the drugs viz. cycloheximide, chloramphenicol, fluconazole and o-phenanthroline, to which CDR1 confers resistance, could also prevent efflux and enhance accumulation to some extent. In conclusion, we show that human steroid hormones could be the substrates for Cdr1p and the energy dependent transport mediated by it is specific for estradiol and corticosterone.
Krishnamurthy
S
S
School of Life Sciences, Jawaharlal Nehru University, New Delhi, India.
Gupta
V
V
Snehlata
P
P
Prasad
R
R
D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D002176:Candida albicans / Q000737:chemistry / Q000235:genetics*; D003345:Corticosterone / Q000493:pharmacokinetics*; D018432:Drug Resistance, Multiple / Q000235:genetics*; D004958:Estradiol / Q000493:pharmacokinetics*; D005656:Fungal Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D026901:Membrane Transport Proteins; D011485:Protein Binding; D012441:Saccharomyces cerevisiae / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
D018528:ATP-Binding Cassette Transporters; C094693:CDR1 protein, Candida albicans; D005656:Fungal Proteins; D026901:Membrane Transport Proteins; D004958:Estradiol; D000255:Adenosine Triphosphate; D003345:Corticosterone